title: Direct thrombin inhibitors and factor xa inhibitors can influence the diluted prothrombin time used as the initial screen for lupus anticoagulant.
abstract: BACKGROUND
  Lupus anticoagulant (LA) is a heterogeneous group of antiphospholipid antibodies. Among others, diluted prothrombin time (dPT) is a sensitive screening test for LA; however, the interpretation of LA tests is difficult in patients treated with anticoagulants. The effect of different types of anticoagulants on the result of LA tests, particularly on dPT, has not been studied extensively.
  
  
  OBJECTIVE
  To determine whether the direct thrombin inhibitors lepirudin and argatroban and the predominantly factor Xa inhibitors enoxaparin, danaparoid, and fondaparinux could interfere with LA screening based on dPT.
  
  
  METHODS
  Each drug was added to normal and LA-positive plasmas in clinically relevant concentrations. Each sample was tested for dPT. Samples with factor Xa inhibitors were investigated before and after addition of heparinase. Mixing and confirmatory tests for LA were not performed.
  
  
  RESULTS
  In the presence of lepirudin or argatroban, dPT increased notably and the dPT ratio exceeded the cutoff value even at subtherapeutic concentrations resulting in false positivity. With increasing factor Xa inhibitor concentrations, a linear increase of dPT ratios and false-positive results were also demonstrated. Although heparinase could almost completely neutralize the anti-Xa effect of all investigated factor Xa inhibitors, dPT ratio returned to the basal level only in case of enoxaparin.
  
  
  CONCLUSIONS
  Here we provide evidence that both the direct thrombin and indirect factor Xa inhibitors influence dPT assay for LA, causing false positivity. This should be considered when interpreting LA results during anticoagulant therapy. However, dPT seems to be a reliable test for LA screening under enoxaparin therapy after neutralization by heparinase.
authors.affiliation: 2nd Department of Medicine, University of Debrecen, 4032 Debrecen, Hungary. zsolah@med.unideb.hu
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Olah
authors.forename: Mariann
authors.initials: M
authors.lastname: Szarvas
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Bereczky
authors.forename: Adrienne
authors.initials: A
authors.lastname: Kerenyi
authors.forename: Janos
authors.initials: J
authors.lastname: Kappelmayer
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Boda
mesh_terms: D000925:Anticoagulants / Q000737:chemistry / Q000494:pharmacology*; D000991:Antithrombins / Q000737:chemistry / Q000494:pharmacology*; D001120:Arginine / Q000031:analogs & derivatives; D002809:Chondroitin Sulfates / Q000737:chemistry / Q000494:pharmacology; D003871:Dermatan Sulfate / Q000737:chemistry / Q000494:pharmacology; D017984:Enoxaparin / Q000737:chemistry / Q000494:pharmacology; D065427:Factor Xa Inhibitors; D005189:False Positive Reactions; D000077425:Fondaparinux; D006497:Heparan Sulfate / Q000737:chemistry / Q000494:pharmacology; D006629:Hirudins / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D016682:Lupus Coagulation Inhibitor / Q000097:blood*; D008403:Mass Screening / Q000379:methods*; D010875:Pipecolic Acids / Q000737:chemistry / Q000494:pharmacology; D011134:Polysaccharides / Q000737:chemistry / Q000494:pharmacology; D011517:Prothrombin Time; D011994:Recombinant Proteins / Q000737:chemistry / Q000494:pharmacology; D013449:Sulfonamides; D013917:Thrombin / Q000737:chemistry / Q000187:drug effects*
chemical_list: D000925:Anticoagulants; D000991:Antithrombins; D001120:Arginine; D002809:Chondroitin Sulfates; D003871:Dermatan Sulfate; D017984:Enoxaparin; D065427:Factor Xa Inhibitors; D000077425:Fondaparinux; D006497:Heparan Sulfate; D006629:Hirudins; D016682:Lupus Coagulation Inhibitor; D010875:Pipecolic Acids; D011134:Polysaccharides; D011994:Recombinant Proteins; D013449:Sulfonamides; D013917:Thrombin; C035838:danaparoid; C031942:argatroban; C083544:lepirudin